Assessing the hazard of death, cardiac tamponade, and pericardial constriction among HIV and tuberculosis pericarditis patients using the extended Cox-hazard model: Intervention study

Background and Aims: Tuberculous (TB) pericarditis (TBP), a TB of the heart, is linked to significant morbidity and mortality rates. Administering glucocorticoid therapy to individuals with TBP might enhance overall results and lower the likelihood of fatality. However, the actual clinical effectiveness of supplementary glucocorticoids remains uncertain. This study specifically evaluated the effects of prednisolone, prednisolone-antiretroviral therapy (ART) interaction, and other potential risk factors in reducing the hazard of the composite outcome, death, cardiac tamponade, and constriction, among TBP and human immunodeficiency virus (HIV) patients. Methods: The data used in this study were obtained from the investigation of the Management of Pericarditis trial, a multicentre international randomized double-blind placebo-controlled 2 x 2 factorial study that investigated the effects of two TB treatments, prednisolone and Mycobacterium indicus pranii immunotherapy in patients with TBP in Africa. This study used a sample size of 587 TBP and HIV-positive patients randomized into prednisolone and its corresponding placebo arm. We used the extended Cox-proportional hazard model to evaluate the effects of the covariates on the hazard of the survival outcomes. Models fitting and parameter estimation were carried out using R version 4.3.1. Results: Prednisolone reduces the hazard of composite outcome (hazrad ratio [HR] = 0.32, 95% confidence interval [CI] = 0.19 , 0.54 $0.19,0.54$, p < 0.001), cardiac tamponade (HR = 0.14, 95% CI = 0.05, 0.42, p < 0.001) and constriction (HR = 0.81, 95% CI = 0.41, 1.61, p = 0.55). However, prednisolone increases the hazard of death (HR = 1.58, 95% CI = 1.11, 2.24, p = 0.01). Consistent usage of ART reduces the hazard of composite outcome, death, and constriction but insignificantly increased the hazard of cardiac tamponade. Conclusion: The study offers valuable insights into how prednisolone impact the hazard of different outcomes in patients with TBP and HIV. The findings hold potential clinical significance, particularly in guiding treatment decisions and devising strategies to enhance outcomes in this specific patient group. However, there are concerns about prednisolone potentially increasing the risk of death due to HIV-related death.